A novel Candida albicans Als3, Hwp1 and Met6 derived complex peptide protects mice against hematogenously induced candidiasis.

Candida albicans can cause superficial or systemic infections in humans, particularly in immunocompromised individuals. Vaccination strategies targeting specific antigens of C. albicans have shown promise in providing protection against invasive candidiasis. This study aimed to evaluate the immuno-protective capacity of a KLH conjugated complex peptide, 3P-KLH, containing epitopes from C. albicans antigens Als3, Hwp1, and Met6 in a murine model of hematogenously induced candidiasis. Mice immunized with 3P-KLH raised a specific antibody response, and protection against C. albicans infection was assessed. Immunized mice exhibited significantly lower fungal load in their kidneys compared to the control group. Moreover, 37.5 % of immunized mice survived 21 days after the infection, while all control animals died within the first nine days. These findings suggest that the 3P-KLH complex peptide, targeting C. albicans key antigens, elicits a protective immune response and reduces the severity of systemic Candida infection. In addition, the high binding affinity of the selected epitopes with MHC II alleles further supports the potential immunogenicity of this peptide in humans. This research provides insights into the development of novel immunotherapeutic approaches against invasive candidiasis.

Candida albicans cDNA library screening reveals novel potential diagnostic targets for invasive candidiasis.

The detection of patterns associated with the invasive form of Candida albicans, such as Candida albicans germ tube antibodies (CAGTA), is a useful complement to blood culture for Invasive Candidiasis (IC) diagnosis. As CAGTA are detected by a non-standardisable and non-automatable technique, a Candida albicans cDNA expression library was screened with CAGTA isolated from serum of an animal model of invasive candidiasis, and five protein targets were identified: hyphally regulated cell wall protein 1 (Hyr1), enolase 1 (Eno1), coatomer subunit gamma (Sec21), a metallo-aminopeptidase (Ape2) and cystathionine gamma-lyase (Cys3). Homology with proteins from other organisms rules out Cys3 as a good biomarker while Sec21 results suggest that it is not in the germ tubes surface but secreted to the external environment. Our analysis propose Ape2, Sec21 and a region of Hyr1 different from the one currently being studied for immunoprotection as potential biomarker candidates for the diagnosis of IC.

Anti-Candida Antibodies of Patients with Invasive Candidiasis Inhibit Growth, Alter Cell Wall Structure, and Kill Candida albicans In Vitro.

Invasive candidiasis (IC), caused by Candida yeasts, particularly Candida albicans, poses a significant threat with high mortality rates. Diagnosis is challenging due to Candida's common presence in human microbiota. To address this, our research group developed an immunofluorescence assay detecting Candida albicans Germ Tube Antibodies (CAGTA) in IC patients. CAGTA, indicative of invasive processes, is associated with a lower mortality rate in ICU patients. Based on this premise, this study aims to provide results regarding the lack of knowledge about the potential activity of CAGTA against invasive infections in humans caused by the fungus Candida albicans. Therefore, in order to characterize the activity of CAGTA produced by patients with IC, we used sera from 29 patients with IC caused by either C. albicans or non-albicans Candida species. Whole serum IgG antibodies were fractionated into anti-blastospores, CAGTA-enriched, and purified CAGTA and the assessments included XTT colorimetric assays for metabolic activity, CFU counts for viability, and microscopy for growth, viability, and morphological analysis. The CAGTA-enriched IgG fraction significantly reduced the metabolic activity and viability of C. albicans compared to anti-blastospores. Purified CAGTA altered germ tube cell wall surfaces, as revealed by electron microscopy, and exhibited fungicidal properties by DiBAC fluorescent staining. In conclusion, antibodies in response to invasive candidiasis have antifungal activity against Candida albicans, influencing metabolic activity, viability, and cell wall structure, leading to cell death. These findings suggest the potential utility of CAGTA as diagnostic markers and support the possibility of developing immunization protocols against Candida infections.

Molecular Identification of Fungal Species through Multiplex-qPCR to Determine Candidal Vulvovaginitis and Antifungal Susceptibility.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting women worldwide. This study aimed to develop a rapid qPCR assay for the accurate identification of VVC etiological agents and reduced azole susceptibility. One hundred and twenty nine vaginal samples from an outpatient clinic (Bilbao, Spain) were analyzed using culture-based methods and a multiplex qPCR targeting fungal species, which identified Candida albicans as the predominant species (94.2%). Antifungal susceptibility tests revealed reduced azole susceptibility in three (3.48%) isolates. Molecular analysis identified several mutations in genes associated with azole resistance as well as novel mutations in TAC1 and MRR1 genes. In conclusion, we developed a rapid multiplex qPCR assay that detects C. albicans in vulvovaginal specimens and reported new mutations in resistance-related genes that could contribute to azole resistance.

Preventing organ damage in systemic lupus erythematosus: the impact of early biological treatment.

INTRODUCTION: One of the most important aims in the management of systemic lupus erythematosus (SLE) is to avoid or delay the accumulation of organ damage. The first five years after diagnosis are crucial for prognosis. AREAS COVERED: This manuscript reviews available data on organ damage accrual in SLE and early therapeutic intervention as a possible strategy to prevent its long-term accrual. EXPERT OPINION: Organ damage can be minimized by controlling disease activity and risk of flares, reducing the dose of glucocorticoids, and ensuring a proper therapeutic intervention with an early introduction of the right therapies. The current standard treatment cannot provide clinical remission in all patients with SLE. Therefore, there is a clinical need for introducing new therapeutic strategies able to achieve the main therapeutic objectives. The addition of biologic and other therapeutic agents to the standard of care is effective for controlling disease activity and for preventing severe flares, enabling a reduced use of glucocorticoids, and presumably reducing organ damage progression. Considering its efficacy and safety, early inclusion of biologic agents in the first lines of the treatment algorithm, at least in certain patients, could be considered as an innovative treatment approach to decrease disease burden in SLE patients.

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Biomarkers for the diagnosis of invasive candidiasis in immunocompetent and immunocompromised patients.

Blood culture methods show low sensitivity, so reliable non-culture diagnostic tests are needed to help clinicians with the introduction, de-escalation, and discontinuation of antifungal therapy in patients with suspected invasive candidiasis (IC). We evaluated different biomarkers for the diagnosis of IC in immunocompetent and immunocompromised patients at risk for developing invasive fungal diseases. The specificity of Candida albicans germ-tube antibodies (CAGTA) detection was high (89%-100%), but sensitivity did not exceed 61% even after raising the cut-off from 1/160 to 1/80. We developed enzyme-linked immunoassays detecting antibodies against C. albicans proteins (Als3-N, Hwp1-N, or Met6) that resulted more sensitive (66%-92%) but less specific than CAGTA assay. The combination of 1,3-beta-D-glucan (BDG) detection and CAGTA results provided the highest diagnostic usefulness in immunocompetent patients. However, in immunocompromised patients, anti-Met6 antibodies was the best biomarker, both, alone or in combination with BDG.

Recommendations for prevention of infection in systemic autoimmune rheumatic diseases. / Recomendaciones SER sobre prevención de infección en enfermedades reumáticas autoinmunes sistémicas.

OBJECTIVES: To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. RESULTS: Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. CONCLUSIONS: There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Aportaciones del registro de lupus de la Sociedad Española de Reumatología (RELESSER) al conocimiento del lupus eritematoso sistémico en España / Contributions of the lupus register of the Spanish Society of Rheumatology (RELESSER) to the knowledge of systemic lupus erythematosus in Spain

El registro de lupus de la Sociedad Española de Reumatología (RELESSER) es un registro multicéntrico de pacientes con lupus eritematoso sistémico seguidos en servicios de reumatología españoles, que contiene cuantiosa información sobre 4.024 pacientes. Hasta la fecha han sido publicados 14 análisis sobre la fase transversal del registro. Se describen los resultados más relevantes, a criterio de los autores, concernientes a las características clínicas acumuladas, nivel de actividad, tratamientos, refractariedad, daño y mortalidad. Se revisan asimismo los resultados de análisis específicos sobre el lupus incompleto, la nefritis lúpica, las manifestaciones respiratorias, los eventos cardiovasculares, las infecciones graves, las neoplasias, la fibromialgia, el lupus en varones, el lupus en latinoamericanos y el lupus de inicio juvenil, comparando los diferentes subgrupos con el total de la cohorte. RELESSER se ha constituido como uno de los registros clínicos de lupus eritematoso sistémico más importantes del mundo, resultando altamente productivo en términos de generación de conocimiento de la enfermedad en pacientes españoles, útil también para toda la comunidad científica.(AU)

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors’ perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.(AU)

Comorbidities (excluding lymphoma) in Sjögren's syndrome.

The information about comorbidities (excluding lymphoma) in primary Sjögren's syndrome (pSS) is relatively scarce. Cardiovascular disease, infections, musculoskeletal conditions or malignancy are likely the most relevant comorbid conditions in pSS. Different infections (particularly oral candidal infections) and fibromyalgia are extremely frequent in the daily clinical practice. On the other hand, the incidence of cardiovascular events and cancer in pSS is low, so information about them comes from large epidemiological studies or meta-analysis. For this reason, preclinical vascular disease is investigated by different techniques, demonstrating the presence of early atherosclerosis in pSS patients. Coronary events could be slightly more frequent in pSS than in the general population. The overall risk of malignancy in pSS patients seems to be slightly increased, likely due to excess occurrence of lymphoma. An association between pSS and thyroid cancer might exist, although it should be confirmed by further investigations.

Contributions of the lupus register of the Spanish Society of Rheumatology (RELESSER) to the knowledge of systemic lupus erythematosus in Spain. / Aportaciones del registro de lupus de la Sociedad Española de Reumatología (RELESSER) al conocimiento del lupus eritematoso sistémico en España.

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors' perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

Sequencing of FKS Hot Spot 1 from Saprochaete capitata To Search for a Relationship to Reduced Echinocandin Susceptibility.

Saprochaete capitata, formerly known as Geotrichum capitatum, is an emerging fungal pathogen with low susceptibility to echinocandins. Here, we report the nucleotide sequence of the S. capitata hot spot 1 region of the FKS gene (FKS HS1), which codifies for the catalytic subunit of ß-1,3-d-glucan synthase, the target of echinocandins. For that purpose, we first designed degenerated oligonucleotide primers derived from conserved flanking regions of the FKS1 HS1 segment of 12 different fungal species. Interestingly, analysis of the translated FKS HS1 sequences of 12 isolates of S. capitata revealed that all of them exhibited the same F-to-L substitution in a position that is highly related to reduced echinocandin susceptibility.

Guía de práctica clínica para el lupus eritematoso sistémico: recomendaciones para el abordaje clínico general / Clinical practice guidelines for systemic lupus erythematosus: Recommendations for general clinical management

El lupus eritematoso sistémico (LES) es una compleja enfermedad reumática multisistémica de origen autoinmune con una morbimortalidad importantes. Es una de las enfermedades autoinmunes más comunes, con una prevalencia estimada de 20-150/100.000 habitantes. El espectro clínico del LES es amplio y variable tanto en manifestaciones clínicas como en gravedad. Esto ha hecho que el Ministerio de Sanidad, Servicios Sociales e Igualdad haya promovido y financiado el desarrollo de una guía de práctica clínica (GPC) sobre el LES dentro del Programa de GPC en el Sistema Nacional de Salud que coordina GuiaSalud. Esta GPC pretende ser el instrumento de referencia en el Sistema Nacional de Salud para dar soporte a la gestión clínica integral de las personas con LES por parte de todos los profesionales sanitarios implicados, independientemente de la especialidad y el nivel asistencial, contribuyendo a homogeneizar y mejorar la calidad de las decisiones clínicas en nuestro entorno con el objetivo de mejorar los resultados de salud de las personas afectadas. En el presente artículo se presentan y discuten las recomendaciones formuladas en relación con el manejo general de la enfermedad, en concreto, el seguimiento clínico, el abordaje terapéutico general, los estilos de vida saludables, la fotoprotección y la formación para los pacientes. Recomendaciones basadas en la mejor evidencia científica disponible y en la discusión y consenso de grupos de expertos (AU)

Systemic lupus erythematosus (SLE) is a complex rheumatic multisystemic disease of autoimmune origin with significant potential morbidity and mortality. It is one of the most common autoimmune diseases with an estimated prevalence of 20-150 cases per 100,000 inhabitants. The clinical spectrum of SLE is wide and variable both in clinical manifestations and severity. This prompted the Spanish Ministry of Health, Social Services and Equality to promote and fund the development of a clinical practice guideline (CPG) for the clinical care of SLE patients within the Programme of CPG in the National Health System which coordinates GuiaSalud. This CPG is is intended as the reference tool in the Spanish National Health System in order to support the comprehensive clinical management of people with SLE by all health professionals involved, regardless of specialty and level of care, helping to standardize and improve the quality of clinical decisions in our context in order to improve the health outcomes of the people affected. The purpose of this document is to present and discuss the rationale of the recommendations on the general management of SLE, specifically, clinical follow-up, general therapeutic approach, healthy lifestyles, photoprotection, and training programmes for patients. These recommendationsare based on the best available scientific evidence, on discussion and the consensus of expert groups (AU)

[Clinical practice guidelines for systemic lupus erythematosus: Recommendations for general clinical management]. / Guía de práctica clínica para el lupus eritematoso sistémico: recomendaciones para el abordaje clínico general.

Systemic lupus erythematosus (SLE) is a complex rheumatic multisystemic disease of autoimmune origin with significant potential morbidity and mortality. It is one of the most common autoimmune diseases with an estimated prevalence of 20-150 cases per 100,000 inhabitants. The clinical spectrum of SLE is wide and variable both in clinical manifestations and severity. This prompted the Spanish Ministry of Health, Social Services and Equality to promote and fund the development of a clinical practice guideline (CPG) for the clinical care of SLE patients within the Programme of CPG in the National Health System which coordinates GuiaSalud. This CPG is is intended as the reference tool in the Spanish National Health System in order to support the comprehensive clinical management of people with SLE by all health professionals involved, regardless of specialty and level of care, helping to standardize and improve the quality of clinical decisions in our context in order to improve the health outcomes of the people affected. The purpose of this document is to present and discuss the rationale of the recommendations on the general management of SLE, specifically, clinical follow-up, general therapeutic approach, healthy lifestyles, photoprotection, and training programmes for patients. These recommendations are based on the best available scientific evidence, on discussion and the consensus of expert groups.

Lo mejor del año en lupus eritematoso sistémico / What is new in systemic lupus erythematosus

El lupus eritematoso sistémico es una enfermedad reumática sistémica enormemente heterogénea, con múltiples posibles manifestaciones de patogenia diversa, como se ilustra en esta revisión sobre las novedades más relevantes concernientes a esta compleja enfermedad autoinmune. Se revisan aspectos como la patogenia de la anemia crónica asociada al lupus eritematoso sistémico, la estimación del riesgo cardiovascular, el síndrome antifosfolipídico, la predicción del daño acumulado y los avances más recientes en el tratamiento, incluyendo los tolerógenos y las terapias biológicas. También se revisan las contribuciones más relevantes en torno a las terapias clásicas, como la optimización del uso de los glucocorticoides y los antipalúdicos, así como el papel que pueda desempeñar la vitamina D (AU)

Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred (AU)

Identification and characterization of nine atypical Candida dubliniensis clinical isolates.

Candida dubliniensis is a pathogenic yeast of the genus Candida closely related to Candida albicans. The phenotypic similarity of these two species often leads to misidentification of C. dubliniensis isolates in clinical samples. DNA-based methods continue to be the most effective means of discriminating accurately between the two species. Here, we report on the identification of nine unusual Candida isolates that showed ambiguous identification patterns on the basis of their phenotypic and immunological traits. The isolates were categorized into two groups. Group I isolates were unable to produce germ tubes and chlamydospores, and to agglutinate commercial latex particles coated with a mAb highly specific for C. dubliniensis. Group II isolates grew as pink and white colonies on CHROMagar Candida and ChromID Candida, respectively. Carbohydrate assimilation profiles obtained with API/ID32C together with PCR amplification with specific primers and DNA sequencing allowed reliable identification of the nine unusual clinical isolates as C. dubliniensis.

What is new in systemic lupus erythematosus.

Systemic lupus erythematosus is a heterogeneous rheumatic systemic disease with extremely varied clinical manifestations and a diverse pathogenesis, as illustrated in this review on the most relevant new knowledge related to the disease. Topics such as anemia, pathogenesis, cardiovascular risk assessment, antiphospholipid syndrome, prediction of damage and recent advances in treatment, including tolerogenic and biological agents, are discussed. Relevant contributions regarding classical therapies such as corticosteroid and antimalarials and their optimal use, as well as the roll of vitamin D, are also referred.